Download A potted history and impact of panel tests

The Gene Dossier a Potted
History
Fiona Stewart
The Start
• Was not very promising
• Quite a lot of hostility to the idea that anyone
would consider telling clinicians or
laboratories who should have genetic tests
and in what circumstances
First meeting of the steering group was on September 17th 2002
Gene Dossier Process
• Laboratory decides it wishes to offer a test
through the UKGTN
• Gene dossier is down loaded from UKGTN
website and completed
• Gene dossier is submitted to UKGTN and is
assessed
• If approved goes onto the directory
The first gene dossier meeting
• Involved the whole steering group
• We were sent 80+ dossiers to consider prior to
the meeting
The meeting
• Probably fair to say there was a general feeling
particularly amongst clinicians that if a test
could ever be offered to anyone in any
circumstances then it should be approved
• No real feeling that we should define who the
test was for and in what circumstances it
might be appropriate to offer it (with a few
exceptions!)
• Pretty much all dossiers approved
Changes
• Realised that it was impractical to have all
GD’s considered by the entire steering group
• Better to have a smaller group to consider the
dossiers
• Those that were approved would then go to
the steering group for endorsement
• A sub group was set up initially called the
Gene Dossier Group now called the Genetic
Test Evaluation Working Group
Composition of GD group
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At least one of the following:
Clinical Geneticist
Clinical Scientist
Commissioner
Public Health
Genetic Counsellor
Patient Representative
UKGTN staff and the UKGTN expert clinical
advisors
Single Gene Testing
• Initially all GD’s were for one gene for one
condition
• Target population defined more carefully
• Clinical indications for the test important
• What was the clinical usefulness of the test?
• What did this information add to the overall
care and management of the patient and their
family
Testing Criteria
• Realised we had to define the population to
whom the test should be offered
• Also realised that there is a huge pressure on
clinicians to offer a wide range of genetic tests to
patients and some guidance about who might
benefit most from the test would be helpful and
might be welcomed by clinicians
• Might also give some supportive evidence for
cases where the clinician feels the test is not
indicated
• Testing criteria were introduced in 2006
Care Pathways
• Very important to know where the genetic
test fits into the investigative pathway
• In conditions where there may be a number of
genetic tests it is helpful to know in which
order genes should be tested and what other
tests and actions might be indicated
• We started to ask laboratories to supply
testing strategies in some cases
• Our priority is to try and make things user
friendly for the clinician
• With the mainstreaming of genetic tests we
know that some users will not be as familiar
with the area of genetics
• Therefore we feel testing strategies and
testing criteria might be very useful
The Ultra Rares
• We realised that a lot of time was being spent
discussing dossiers for tests which might only
be applicable to less than 5 patients per year
• These tests are now first assessed by the
expert advisors and come to the group for
endorsement of their decision.
Panel Tests
• We are receiving an increasing number of
panel tests
• These tests tend to use next generation
sequencing and can look at a number of genes
at once
• They are particularly useful for conditions
where a number of different genes can give a
very similar if not identical clinical picture e.g.
Retinitis pigmentosa
Costs
• Although the cost of the panel test may be
higher than a single gene test they may avoid
the need for serial genetic testing
• A good example is hereditary sensory motor
neuropathy. If an affected individual does not
have the common PMP22 duplication then
serial testing of all the other genes, each of
which may have a low pick up rate, can be
very costly
Advantages to Patients
• It can be very time consuming to test genes
sequentially so an ‘all at once’ strategy can
provide a more rapid result for the patient
Important points
• Coverage may not be optimal for all the genes
so if there is clear indication that a single gene
is likely to responsible it is best to test for that
first
• If a mutation is found then family follow up
and/or prenatal diagnosis would be done
using the single gene test not the panel test
The future.....
• More panel tests
• Whole exome sequencing
• Whole genome sequencing
Principles
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Right patient
Right test
Right time
These principles hold true whatever
methodology is available now or in the future
Special thanks to all the members of the
Genetic Testing and Evaluation Working
Group who have spent many happy hours
pouring over gene dossiers
Also thanks to the expert advisors Mark ,
Su and Shehla who are truly experts and
whose input is invaluable
Finally thanks to Peta , Jacqui and Jane
plus other members of the UKGTN who
have provided such great support over the
years